Development of a technology to certify engineered DNA molecules

开发验证工程 DNA 分子的技术

• 批准号: 10509988
• 负责人: Jean M Peccoud
• 金额: $ 38.8万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10509988
• 关键词: Address; Affect; Algorithms; Architecture; Bar Codes; Biological; Biological Process; Biological Sciences; Biological Testing; Biology; Biomedical Research; Biotechnology; Blood Circulation; Cell Therapy; Certification; Clinical Research; Code; Communities; Complex; Computer Security; Computers; DNA; DNA Sequence; Data; Database Management Systems; Development; Documentation; Elements; Engineering; Ensure; Event; Fostering; Funding; Gene Expression; Generations; Genetic; Genetic Engineering; Genome engineering; Individual; Industry; Infrastructure; Knowledge; Label; Link; Methodology; Methods; Modification; Molecular; Mutate; Mutation; Names; Persons; Pharmaceutical Preparations; Plasmids; Play; Production; Property; Publications; Recombinants; Recording of previous events; Records; Reproducibility; Research; Resources; Role; Safety; Scheme; Scientist; Secure; Security; Signal Transduction; Software Engineering; Standardization; System; Technology; Testing; Therapeutic; Tube; United States National Institutes of Health; Validation; Variant; Visualization software; Writing; base; bioinformatics pipeline; biological research; computer network; cryptography; design; digital; engineering design; expression vector; follow-up; gene therapy; genetic element; improved; innovation; medical specialties; new technology; online resource; research and development; response; technology validation; therapeutic protein; tool; vaccine development; web site

PROJECT SUMMARY The open availability of authenticated, well-documented research materials is essential for scientific progress. Plasmids have become essential research tools to address almost any question in biology, and together with other forms of engineered DNA molecules, are essential for clinical research applications including gene therapy, vaccine development, and the production of recombinant drugs. Currently, the two common links between a plasmid and its documentation are the plasmid names and the plasmid sequence. Despite the central role that plasmids play in biomedical research and development, there is no guaranteed way to connect a physical plasmid in a tube to its documentation. A pipetting error, a labelling error, a spontaneous mutation, or an undocumented modification of the plasmid are some of the events that could result in a tube containing a different plasmid than what is indicated on the label. In addition, there is no standardized, secure approach to documenting the sequence, function, and lineage of a plasmid. As a result, there are widespread discrepancies between the physical sequences of the plasmids in circulation in the life science community and their supposed reference sequence. This situation creates reproducibility issues, slows down R&D efforts and raises significant security and safety issues for biotechnology applications. We are proposing to develop a new digital certificate technology, enabled by a web-based resource called MyPlasmid.org, that will provide a robust, physical link between engineered DNA molecules, their electronic documentation, and their authors. This technology will produce unique DNA sequences generated by cryptographic algorithms that can be inserted into an engineered DNA molecule. MyPlasmid.org will allow users to document their genetic designs by aggregating the documentation of individual genetic elements as well as combinations of elements. In addition, it will link the computer records of the engineered DNA sequence directly to the molecule itself and provide a method to retrieve documentation without a priori knowledge of the plasmid's identity. Short unique DNA sequences called certificates will be inserted between the functional blocks of engineered sequences. Unlike DNA barcodes, certificates will be computed by cryptographic algorithms using the DNA sequence itself and the author's identity as input so that users of engineered DNA molecules can verify the origin and integrity of certified DNA molecules. The technology described in this proposal is expected to foster a transition similar what has been observed in the semi-conductor industry where different stakeholders invest in the development of circuits that can be easily combined in larger designs that can then be manufactured by foundries not involved in the chip design. By ensuring that the sequence, origin, function, and lineage of engineered DNA molecules is accurately tracked and conveyed to all users, the proposed technology will improve the reproducibility, utility, and potential application of engineered DNA molecules in the life sciences.

项目概要 公开提供经过验证、记录齐全的研究材料对于科学进步至关重要。 质粒已成为解决几乎所有生物学问题的重要研究工具，并且与 其他形式的工程 DNA 分子对于临床研究应用至关重要，包括基因治疗、 疫苗开发和重组药物的生产。目前，a 之间的两个常见链接 质粒及其文档是质粒名称和质粒序列。尽管发挥着核心作用 质粒在生物医学研究和开发中发挥作用，但没有保证的方法可以连接物理 管中的质粒及其文档。移液错误、标记错误、自发突变或 未记录的质粒修饰是一些可能导致管中含有不同的物质的事件。 质粒比标签上所示的要多。此外，没有标准化、安全的方法来 记录质粒的序列、功能和谱系。结果，出现了广泛的差异 生命科学界中流通的质粒的物理序列与其假设的之间 参考序列。这种情况会产生可重复性问题，减慢研发工作并引发重大问题 生物技术应用的安全和保障问题。 我们提议开发一种新的数字证书技术，由称为 MyPlasmid.org，它将在工程 DNA 分子、其电子 文档及其作者。该技术将产生独特的 DNA 序列 可以插入到工程 DNA 分子中的加密算法。 MyPlasmid.org 将允许用户 通过汇总单个遗传元素的记录来记录其遗传设计以及 元素的组合。此外，它将直接链接工程DNA序列的计算机记录 分子本身，并提供一种在不先验了解质粒的情况下检索文档的方法 身份。称为证书的短的独特 DNA 序列将被插入到 工程序列。与 DNA 条形码不同，证书将使用加密算法计算得出 DNA 序列本身和作者的身份作为输入，以便工程 DNA 分子的用户可以验证 经认证的 DNA 分子的起源和完整性。该提案中描述的技术预计将 促进类似于半导体行业观察到的转变，不同的利益相关者 投资开发可以轻松组合到更大设计中的电路，然后进行制造 由不参与芯片设计的代工厂设计。通过确保序列、起源、功能和谱系 工程DNA分子被准确跟踪并传送给所有用户，所提出的技术将 提高工程 DNA 分子在生命科学中的可重复性、实用性和潜在应用。